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PMID: 22615553 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Reconstruction of genome-scale active metabolic networks for 69 human cell types and 16 cancer types using INIT.

PLoS computational biology ·Vol. 8 ·No. 5 ·2012-00-00 ·Pages e1002518

Agren R, Bordel S, Mardinoglu A, Pornputtapong N, Nookaew I, Nielsen J

Abstract

Development of high throughput analytical methods has given physicians the potential access to extensive and patient-specific data sets, such as gene sequences, gene expression profiles or metabolite footprints. This opens for a new approach in health care, which is both personalized and based on system-level analysis. Genome-scale metabolic networks provide a mechanistic description of the relationships between different genes, which is valuable for the analysis and interpretation of large experimental data-sets. Here we describe the generation of genome-scale active metabolic networks for 69 different cell types and 16 cancer types using the INIT (Integrative Network Inference for Tissues) algorithm. The INIT algorithm uses cell type specific information about protein abundances contained in the Human Proteome Atlas as the main source of evidence. The generated models constitute the first step towards establishing a Human Metabolic Atlas, which will be a comprehensive description (accessible online) of the metabolism of different human cell types, and will allow for tissue-level and organism-level simulations in order to achieve a better understanding of complex diseases. A comparative analysis between the active metabolic networks of cancer types and healthy cell types allowed for identification of cancer-specific metabolic features that constitute generic potential drug targets for cancer treatment.

MeSH Terms
Algorithms Animals Chromosome Mapping/methods Computer Simulation Databases, Protein Humans Metabolome Models, Biological Neoplasms/genetics,metabolism Proteome/genetics,metabolism Signal Transduction
Chemicals
Proteome
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Agren Rasmus
Department of Chemical and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.
Bordel Sergio
Mardinoglu Adil
Pornputtapong Natapol
Nookaew Intawat
Nielsen Jens
References (43)
43 references, click to expand
  1. Fifteen years of large scale metabolic modeling of yeast: developments and impacts.
    Biotechnol Adv. 2012 Sep-Oct;30(5):979-88 PMID: 21846501
  2. A protocol for generating a high-quality genome-scale metabolic reconstruction.
    Nat Protoc. 2010 Jan;5(1):93-121 PMID: 20057383
  3. Pharmaceutical interventions for obesity: a public health perspective.
    Diabetes Obes Metab. 2011 Jun;13(6):490-7 PMID: 21205125
  4. Thirty years of polyamine-related approaches to cancer therapy. Retrospect and prospect. Part 2. Structural analogues and derivatives.
    Curr Drug Targets. 2003 Oct;4(7):565-85 PMID: 14535655
  5. The growing scope of applications of genome-scale metabolic reconstructions using Escherichia coli.
    Nat Biotechnol. 2008 Jun;26(6):659-67 PMID: 18536691
  6. Cyclooxygenases and lipoxygenases in cancer.
    Cancer Metastasis Rev. 2011 Dec;30(3-4):277-94 PMID: 22002716
  7. Network-based prediction of human tissue-specific metabolism.
    Nat Biotechnol. 2008 Sep;26(9):1003-10 PMID: 18711341
  8. Geranylgeranyltransferase I as a target for anti-cancer drugs.
    J Clin Invest. 2007 May;117(5):1223-5 PMID: 17476354
  9. Otto Warburg's contributions to current concepts of cancer metabolism.
    Nat Rev Cancer. 2011 May;11(5):325-37 PMID: 21508971
  10. HepatoNet1: a comprehensive metabolic reconstruction of the human hepatocyte for the analysis of liver physiology.
    Mol Syst Biol. 2010 Sep 7;6:411 PMID: 20823849
  11. Effect of methylglyoxal on human leukaemia 60 cell growth: modification of DNA G1 growth arrest and induction of apoptosis.
    Leuk Res. 1996 May;20(5):397-405 PMID: 8683979
  12. Computational prediction of human metabolic pathways from the complete human genome.
    Genome Biol. 2005;6(1):R2 PMID: 15642094
  13. Global reconstruction of the human metabolic network based on genomic and bibliomic data.
    Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1777-82 PMID: 17267599
  14. Insight into human alveolar macrophage and M. tuberculosis interactions via metabolic reconstructions.
    Mol Syst Biol. 2010 Oct 19;6:422 PMID: 20959820
  15. Codon usage variability determines the correlation between proteome and transcriptome fold changes.
    BMC Syst Biol. 2011 Feb 25;5:33 PMID: 21352515
  16. Methylglyoxal toxicity in mammals.
    Toxicol Lett. 1994 Jul;73(1):3-24 PMID: 8042200
  17. Context-specific metabolic networks are consistent with experiments.
    PLoS Comput Biol. 2008 May 16;4(5):e1000082 PMID: 18483554
  18. iAB-RBC-283: A proteomically derived knowledge-base of erythrocyte metabolism that can be used to simulate its physiological and patho-physiological states.
    BMC Syst Biol. 2011 Jul 12;5:110 PMID: 21749716
  19. BioGPS: an extensible and customizable portal for querying and organizing gene annotation resources.
    Genome Biol. 2009;10(11):R130 PMID: 19919682
  20. Uncovering transcriptional regulation of metabolism by using metabolic network topology.
    Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2685-9 PMID: 15710883
  21. Towards a knowledge-based Human Protein Atlas.
    Nat Biotechnol. 2010 Dec;28(12):1248-50 PMID: 21139605
  22. The levelling off of the obesity epidemic since the year 1999--a review of evidence and perspectives.
    Obes Rev. 2010 Dec;11(12):835-46 PMID: 20973911
  23. Altered expression of 15-hydroxyprostaglandin dehydrogenase in tumor-infiltrated CD11b myeloid cells: a mechanism for immune evasion in cancer.
    J Immunol. 2009 Jun 15;182(12):7548-57 PMID: 19494278
  24. Farnesyltransferase and geranylgeranyltransferase I inhibitors and cancer therapy: lessons from mechanism and bench-to-bedside translational studies.
    Oncogene. 2000 Dec 27;19(56):6584-93 PMID: 11426643
  25. A human protein atlas for normal and cancer tissues based on antibody proteomics.
    Mol Cell Proteomics. 2005 Dec;4(12):1920-32 PMID: 16127175
  26. Biliverdin reductase: a major physiologic cytoprotectant.
    Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16093-8 PMID: 12456881
  27. A genecentric Human Protein Atlas for expression profiles based on antibodies.
    Mol Cell Proteomics. 2008 Oct;7(10):2019-27 PMID: 18669619
  28. A gene atlas of the mouse and human protein-encoding transcriptomes.
    Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):6062-7 PMID: 15075390
  29. Thirty years of polyamine-related approaches to cancer therapy. Retrospect and prospect. Part 1. Selective enzyme inhibitors.
    Curr Drug Targets. 2003 Oct;4(7):537-64 PMID: 14535654
  30. The BRENDA Tissue Ontology (BTO): the first all-integrating ontology of all organisms for enzyme sources.
    Nucleic Acids Res. 2011 Jan;39(Database issue):D507-13 PMID: 21030441
  31. Systems biology of lipid metabolism: from yeast to human.
    FEBS Lett. 2009 Dec 17;583(24):3905-13 PMID: 19854183
  32. HMDB: the Human Metabolome Database.
    Nucleic Acids Res. 2007 Jan;35(Database issue):D521-6 PMID: 17202168
  33. Geranylgeranyl diphosphate depletion inhibits breast cancer cell migration.
    Invest New Drugs. 2011 Oct;29(5):912-20 PMID: 20480384
  34. [Methylglyoxal--test for biological dysfunctions of homeostasis and endoecology, low cytosolic glucose level, and gluconeogenesis from fatty acids].
    Ter Arkh. 2010;82(10):71-7 PMID: 21341469
  35. Predicting selective drug targets in cancer through metabolic networks.
    Mol Syst Biol. 2011 Jun 21;7:501 PMID: 21694718
  36. KEGG for linking genomes to life and the environment.
    Nucleic Acids Res. 2008 Jan;36(Database issue):D480-4 PMID: 18077471
  37. Pvclust: an R package for assessing the uncertainty in hierarchical clustering.
    Bioinformatics. 2006 Jun 15;22(12):1540-2 PMID: 16595560
  38. Induction of autophagy by spermidine promotes longevity.
    Nat Cell Biol. 2009 Nov;11(11):1305-14 PMID: 19801973
  39. Large-scale in silico modeling of metabolic interactions between cell types in the human brain.
    Nat Biotechnol. 2010 Dec;28(12):1279-85 PMID: 21102456
  40. Compartmentalization of the Edinburgh Human Metabolic Network.
    BMC Bioinformatics. 2010 Jul 22;11:393 PMID: 20649990
  41. Computational reconstruction of tissue-specific metabolic models: application to human liver metabolism.
    Mol Syst Biol. 2010 Sep 7;6:401 PMID: 20823844
  42. Drug off-target effects predicted using structural analysis in the context of a metabolic network model.
    PLoS Comput Biol. 2010 Sep 23;6(9):e1000938 PMID: 20957118
  43. The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models.
    Bioinformatics. 2003 Mar 1;19(4):524-31 PMID: 12611808
Article Info
Journal
PLoS computational biology
Abbr.
PLoS Comput Biol
ISSN
1553-7358
Published
2012-00-00
Epub
2012-00-17
Pages
e1002518
Language
English
Region
United States
NLM ID
101238922
PMCID
PMC3355067
Subset
IM
Analysis Services
Analysis Services

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